The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess.
Bottom Line: We further demonstrate that a HapX homodimer and the CCAAT-binding complex (CBC) cooperatively bind an evolutionary conserved DNA motif in a target promoter.The latter reveals the mode of discrimination between general CBC and specific HapX/CBC target genes.Collectively, our study uncovers a novel regulatory mechanism mediating both iron resistance and adaptation to iron starvation by the same transcription factor complex with activating and repressing functions depending on ambient iron availability.
Affiliation: Division of Molecular Biology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.Show MeSH
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Mentions: Similar to A. fumigatus, HapX orthologs repress iron-dependent pathways and the cccA orthologs during iron starvation in A. nidulans, F. oxysporum, S. pombe, C. neoformans, and C. albicans (Mercier et al, 2006; Hortschansky et al, 2007; Jung et al, 2010; Schrettl et al, 2010; Hsu et al, 2011; Lopez-Berges et al, 2012). Here, we found that HapX-deficiency also impairs growth of A. nidulans and F. oxysporum on high-iron media (Fig7) demonstrating that the function of HapX in iron detoxification is evolutionary conserved. Inspection of genome-wide transcriptional profiling data indicated that the cccA ortholog FOXG_04047 in F. oxysporum is repressed similar to A. fumigatus during iron starvation and upregulated during iron sufficiency in a HapX-dependent manner (Lopez-Berges et al, 2012). These data suggest that in F. oxysporum the decreased iron resistance caused by HapX-deficiency also results from impaired vacuolar iron storage.
Affiliation: Division of Molecular Biology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.